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Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116)

《医学前沿(英文)》 doi: 10.1007/s11684-023-1037-3

摘要: The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir–ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir–ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir–ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China’s homegrown anti-COVID-19 drugs.

关键词: COVID-19     antiviral drugs     mindeudesivir    

Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

Weibao Song, Hongjuan Zhang, Yu Zhang, Rui Li, Yanxing Han, Yuan Lin, Jiandong Jiang

《医学前沿(英文)》 2021年 第15卷 第3期   页码 404-415 doi: 10.1007/s11684-021-0834-9

摘要: Zika virus (ZIKV) is an emerging pathogen associated with neurological complications, such as Guillain–Barré syndrome in adults and microcephaly in fetuses and newborns. This mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid dissemination. However, the development of antivirals against ZIKV is lagging. Although various strategies have been used to study anti-ZIKV agents, approved drugs or vaccines for the treatment (or prevention) of ZIKV infections are currently unavailable. Repurposing clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV infections. The well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical, safe, and efficacious approach to address ZIKV infections. This review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical drugs. Their characteristics, targets, and potential use in anti-ZIKV therapy are presented. This review provides an update and some successful strategies in the search for anti-ZIKV agents are given.

关键词: Zika virus     clinical drugs     ZIKV inhibitors     antivirals     repurposing    

Direct acting antiviral-induced dynamic reduction of serum

Tung Huynh, Ke-Qin Hu

《医学前沿(英文)》 2019年 第13卷 第6期   页码 658-666 doi: 10.1007/s11684-019-0707-7

摘要: Direct acting antiviral (DAA) treatments may reduce the elevated α fetoprotein (AFP), but data on how these treatments affect elevated AFP in patients with chronic hepatitis C (CHC) remain insufficient. In the present study, the frequency of baseline AFP elevations and their related factors, AFP dynamics during and after DAA treatment, and factors associated with AFP reduction was assessed. This retrospective study included 141 patients with CHC without hepatocellular carcinoma who received DAA and achieved sustained virological response. The details are as follows: mean post-treatment follow-up was 99 weeks (12–213); mean age, 57.8 years old; 52%, males; 79%, genotype (GT) 1; and 47%, cirrhosis. Pre-treatment AFP elevation (>5.5 ng/mL) was seen in 48.2% patients. On multivariate analysis, baseline AFP>5.5 was associated with the presence of cirrhosis ( =0.001), co-existing non-alcoholic steatohepatitis (NASH) ( = 0.035), and GT 1 ( = 0.029). AFP normalization was seen in 28.2% patients at treatment week 2, in 52% at the end of treatment, and in 73.4% at the end of follow-up. Post-treatment week 24 AFP normalization was associated with the absence of cirrhosis ( = 0.003), Child–Pugh score<6 ( = 0.015), and baseline AFP<10 ( = 0.015). AFP elevation is common in patients with CHC and independently associated with NASH, cirrhosis, and GT 1. DAA treatment resulted in AFP normalization as early as treatment week 2. Post-treatment week 24 AFP normalization is independently associated with the absence of cirrhosis, Child–Pugh score<6, and baseline AFP<10.

关键词: chronic hepatitis C     α fetoprotein     direct acting antiviral treatment     cirrhosis    

ROUTE DEVELOPMENT, ANTIVIRAL STUDIES, FIELD EVALUATION AND TOXICITY OF AN ANTIVIRAL PLANT PROTECTANT

《农业科学与工程前沿(英文)》 2022年 第9卷 第1期 doi: 10.15302/J-FASE- 2021390

摘要:

It has previously been shown that tryptophan, the biosynthesis precursor of Peganum harmala alkaloids, and its derivatives have anti-TMV activity both in vitro and in vivo. Further exploration of this led to the identification of NK0238 as a highly effective agent for the prevention and control of diseases caused by plant viruses, but the existing routes are unsuitable for its large-scale synthesis. This study optimized a route for two-step synthesis of this virucide candidate via reaction of l-tryptophan with triphosgene to produce l-tryptophan-N-carboxylic anhydride, which then reacts with n-octylamine to give NK0238 at up to 94% yield and nearly 97% HPLC purity. In addition, the route was used for the preparation of NK0238 on a>40 g scale permitting further assessment of its antivirus activity in the greenhouse and field experiments, and toxicity tests. NK0238 exhibited useful antiviral activities against a variety of viruses both in greenhouse and field experiments. The toxicity tests showed that NK0238 was not acutely toxic to birds, fish, honey bees and silkworms. The optimized route provides a solid foundation for its large-scale synthesis and subsequent efficacy and toxicity studies, its excellent activity and safety make NK0238 a promising drug candidate for further development.

 

关键词: antiviral plant protectant / antiviral in the greenhouse / field evaluation / l-trp-NCA / synthesis optimization / toxicity tests    

Design, synthesis, and antiviral properties of 2-aryl-1H-benzimidazole-4-carboxamide derivatives

Xianjin LUO, Zhonglü ZHANG, Yutian YANG, Fei XUE, Naiyun XIU, Yuanbin SHE

《化学科学与工程前沿(英文)》 2009年 第3卷 第3期   页码 305-309 doi: 10.1007/s11705-009-0021-z

摘要: A series of new benzimidazole derivatives were designed and synthesized. Their chemical structures were testified by H NMR, infrared spectroscopy (IR), mass spectrography (MS), and elemental analysis. Their potent antiviral properties indicated the prospect of new drugs. Compound , , , , , , and were identified as novel antivirus with much better selective activity and inhibitory activity than the comparable ribavirin against Coxsackie virus B in VERO cells.

关键词: benzimidazole     coxsackie virus B3     antiviral properties    

ROUTE DEVELOPMENT, ANTIVIRAL STUDIES, FIELD EVALUATION AND TOXICITY OF AN ANTIVIRAL PLANT PROTECTANT

Wentao XU, Hao TIAN, Hongjian SONG, Yuxiu LIU, Yongqiang LI, Qingmin WANG

《农业科学与工程前沿(英文)》   页码 110-119 doi: 10.15302/J-FASE-2021390

摘要: It has previously been shown that tryptophan, the biosynthesis precursor of alkaloids, and its derivatives have anti-TMV activity both and . Further exploration of this led to the identification of NK0238 as a highly effective agent for the prevention and control of diseases caused by plant viruses, but the existing routes are unsuitable for its large-scale synthesis. This study optimized a route for two-step synthesis of this virucide candidate via reaction of L-tryptophan with triphosgene to produce L-tryptophan- -carboxylic anhydride, which then reacts with -octylamine to give NK0238 at up to 94% yield and nearly 97% HPLC purity. In addition, the route was used for the preparation of NK0238 on a > 40 g scale permitting further assessment of its antivirus activity in the greenhouse and field experiments, and toxicity tests. NK0238 exhibited useful antiviral activities against a variety of viruses both in greenhouse and field experiments. The toxicity tests showed that NK0238 was not acutely toxic to birds, fish, honey bees and silkworms. The optimized route provides a solid foundation for its large-scale synthesis and subsequent efficacy and toxicity studies, its excellent activity and safety make NK0238 a promising drug candidate for further development.

关键词: antiviral plant protectant     antiviral in the greenhouse     field evaluation     L-trp-NCA     synthesis optimization     toxicity tests    

Occurrence, distribution and risk assessment of abused drugs and their metabolites in a typical urban

Peng Hu, Changsheng Guo, Yan Zhang, Jiapei Lv, Yuan Zhang, Jian Xu

《环境科学与工程前沿(英文)》 2019年 第13卷 第4期 doi: 10.1007/s11783-019-1140-5

摘要:

We developed a method for determining 11 abused drugs in water and sediment.

METH and EPH were the dominant drugs in water and sediment in Beiyunhe River.

Abuse drugs in Beiyunhe River were mainly from hospitals and sewage effluents.

Abused drugs in the water would not impair the aquatic ecosystem biologically.

关键词: Drugs of abuse     Occurrence     Distribution     Urban river     Environmental risk    

Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

《农业科学与工程前沿(英文)》 2017年 第4卷 第3期   页码 260-267 doi: 10.15302/J-FASE-2016116

摘要: The innate immune response is the first line of defense against viral invasion and pro-inflammatory chemokines and cytokines have a critical function in the innate immune responses against virus infections. The ability of a rabies virus (RABV) to induce the expression of chemokines and cytokines can lead to viral clearance from the central nervous system (CNS), whereas the ability to evade such expression and activation contributes to virulence and pathogenicity. In this review, the crucial contribution of chemokines/cytokines to clearing RABV from the CNS is discussed, including recruiting leukocytes into the CNS, enhancement of blood brain barrier permeability and activation of various immune cells that are essential for viral clearance. In addition, recombinant RABV expressing cytokines and chemokines can induce elevated innate and adaptive immune responses which result in clearing an established wild-type RABV infection in the CNS.

关键词: antiviral     blood brain barrier     chemokines and cytokines     innate immunity     rabies virus    

ANTIVIRAL EFFECTS OF BACTERIOCIN AGAINST ANIMAL-TO-HUMAN TRANSMITTABLE MUTATED SARS-COV-2: A SYSTEMATIC

《农业科学与工程前沿(英文)》 2021年 第8卷 第4期   页码 603-622 doi: 10.15302/J-FASE -2021397

摘要:

The COVID-19 infections caused by SARS-CoV-2 have resulted in millions of people being infected and thousands of deaths globally since November 2019. To date, no unique therapeutic agent has been developed to slow the progression of this pandemic. Despite possessing antiviral traits the potential of bacteriocins to combat SARS-CoV-2 infection has not been fully investigated. This review summarizes the mechanisms by which bacteriocins can be manipulated and implemented as effective virus entry blockers with infection suppression potential properties to highly transmissible viruses through comprehensive immune modulations that are potentially effective against COVID-19. These antimicrobial peptides have been suggested as effective antiviral therapeutics and therapeutic supplements to prevent rapid virus transmission. This review also provides a new insight into the cellular and molecular alterations which have made SARS-CoV-2 self-modified with diversified infection patterns. In addition, the possible applications of antimicrobial peptides through both natural and induced mechanisms in infection prevention perspectives on changeable virulence cases are comprehensively analyzed. Specific attention is given to the antiviral mechanisms of the molecules along with their integrative use with synthetic biology and nanosensor technology for rapid detection. Novel bacteriocin based therapeutics with cutting-edge technologies might be potential substitutes for existing time-consuming and expensive approaches to fight this newly emerged global threat.

 

关键词: antimicrobial proteins / antiviral profiling of bacteriocins / antiviral therapeutics / immunomodulation / nanosensor technology / mutated SARS-CoV-2    

Chinese expert consensus on oral drugs for the treatment of mature B-cell lymphomas (2020 edition)

《医学前沿(英文)》 2022年 第16卷 第5期   页码 815-826 doi: 10.1007/s11684-021-0891-0

摘要: Oral drugs such as ibrutinib play an important role in the treatment of mature B-cell lymphoma (BCL) due to their reliable efficacy, manageable safety, high accessibility, and convenience for use. Still, no guidelines or consensus focusing on oral drug therapies for BCL is available. To provide a reference of oral agent-based treatment for mature BCL, a panel of experts from the Lymphocyte Disease Group, Chinese Society of Hematology, Chinese Medical Association conducted an extensive discussion and reached a consensus on oral drugs for Chinese BCL patients on the basis of the current application status of oral drugs in China, combined with the latest authoritative guidelines in the world and current research reports. This consensus reviewed the application of oral drugs in the treatment of BCL and the latest research and provided appropriate recommendations on the use of oral drugs for indolent or aggressive BCL patients. With the deepening of research and the development of standardized clinical applications, oral medications will bring better treatment to BCL patients, enabling more patients to benefit from them.

关键词: B-cell lymphoma     oral drug     targeted therapy     immunotherapy     COVID-19 pandemic    

nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleic acid drugs

Vaibhav Mundra, Ram I. Mahato

《化学科学与工程前沿(英文)》 2014年 第8卷 第4期   页码 387-404 doi: 10.1007/s11705-014-1457-3

摘要: There are many challenges in developing efficient and target specific delivery systems of small molecule and nucleic acid drugs. Cell membrane presents one of the major barriers for the penetration of hydrophilic macromolecules across the plasma membrane. Nanocarriers have been designed to enhance their cellular uptake via endocytosis but following their cellular uptake, endosomal escape is the rate limiting step which restricts the value associated with the enhanced uptake by nanocarriers. Viruses are an excellent model for efficient cytosolic delivery by nanocarriers. Viruses exploit intracellular cues to release the genome to cytosol. In this review, we first discuss different endocytic uptake pathways and endosomal escape mechanisms. We then summarize the existing tools for studying the intracellular trafficking of nanocarriers. Finally, we highlight the important design elements of recent virus-based nanocarriers for efficient cellular uptake and endosomal escape.

关键词: nanocarrier     cellular uptake     endosomal release     nucleic acid drug    

Current recommendations of managing HBV infection in preconception or pregnancy

null

《医学前沿(英文)》 2014年 第8卷 第2期   页码 158-165 doi: 10.1007/s11684-014-0340-4

摘要:

Hepatitis B remains a leading cause of cirrhosis, hepatocellular carcinoma and liver transplantation worldwide. Management of chronic hepatitis B during pregnancy is challenging. Transmission of hepatitis B to infants still occurs perinatally although immunoprophylaxis is widely available for infants born to mothers with chronic hepatitis B infection. The emerging data suggest that initiation of antiviral therapy in the beginning of the third trimester in highly viremic mothers can prevent immunoprophylaxis failure in their infants. The available drug safety data show that lamivudine, telbivudine and tenofovir are generally safe to be used during the pregnancy. In order to minimize the fetal exposure to the antiviral medication, antiviral therapy during the pregnancy should be limited to a selected group of patients with cirrhosis, high hepatitis B viral load, or prior history immunoprophylaxis failure. An elective Caesarean section may reduce the risk of perinatal transmission. For those females planning for pregnancy or in early stage of pregnancy, communication and follow-up among obstetrician, gastroenterologist, and primary care physician are important. In this article, we will review the features of hepatitis B infection before, during and after the pregnancy; the risk factors that increase mother-to-child transmission; safety data on antiviral drug use during pregnancy; and the potential role of Caesarean section in selected cases.

关键词: antiviral therapy     Caesarean section     cirrhosis     hepatitis B     immunoprophylaxis     mother-to-child transmission     pregnancy     prevention    

Oral administration of

Sufen ZHAO,Yuanyuan JIA,Weiwei ZHANG,Lili WANG,Yunfei MA,Kedao TENG

《农业科学与工程前沿(英文)》 2015年 第2卷 第4期   页码 318-326 doi: 10.15302/J-FASE-2015080

摘要: Garlic ( Liliaceae) has been safely used for more than 5000 years, and research on garlic extract is rapidly increasing because of its multiple biological functions. The effects of oral administration of garlic mixture (GM, water-soluble extract) on infectious bursal disease virus (IBDV)-infected specific pathogen free male white leghorn chicken were examined through histopathological, immunohistochemical, and Western blot analyses, and enzyme-linked immunosorbent assay. The results confirmed the protective effects of oral administration of 5 mg·kg BW GM (Group GM1) on bursal lesions after IBDV infection. In particular, protein expression of IBDV in the bursa decreased in Group GM1, indicating that GM administration decreased IBDV replication in the bursa. Furthermore, immunoglobulin M- and A-bearing B lymphocytes significantly increased 7 days post infection in bursae in Group GM1 ( <0.01), suggesting that the oral administration of 5 mg·kg GM offers moderate protection against B cell destruction after IBDV infection. During infection, the concentration of bursal interferon gamma (IFN-g) increased and peaked in Group GM1 earlier than in Group T (IBDV-exposed), demonstrating that GM administration prompted the production of IFN-g to protect against IBDV infection.

关键词: garlic     infectious bursal disease virus (IBDV)     antiviral effect     IgM-bearing B lymphocyte    

Telomeric impact of conventional chemotherapy

null

《医学前沿(英文)》 2013年 第7卷 第4期   页码 411-417 doi: 10.1007/s11684-013-0293-z

摘要:

The increased level of chromosome instability in cancer cells, leading to aneuploidy and gross chromosomal rearrangements, is not only a driving force for oncogenesis but also can be the Achille’s heel of the disease since many chemotherapies (CT) kill cells by inducing a non-tolerable rate of DNA damage. A wealth of published evidence showed that telomere stability can be more affected than the bulk of the genome by several conventional antineoplasic drugs. These results raise the interesting possibility that CT with genotoxic drugs preferentially target telomeres. In agreement with this view, accelerated shortening of telomere length has been described in blood lineage cells following high-dose CT (stem cell transplantation) or non-myeloablative CT. However, almost nothing is known on the consequences of this shortening in terms of telomere stability, senescence and on the development of second cancers or post-treatment aging-like syndromes in cancer survivors (cognitive defect, fertility impairment, etc.). In this article, we propose: (1) telomeres of cancer cells are preferential genomic targets of chemotherapies altering chromosome maintenance; (2) telomere functional parameters can be a surrogate marker of chemotherapy sensitivity and toxicity; (3) the use of anti-telomere molecule could greatly enhance the sensitivity to standards chemotherapies.

关键词: telomere     antineoplasic drugs     conventional chemotherapies    

标题 作者 时间 类型 操作

Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116)

期刊论文

Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

Weibao Song, Hongjuan Zhang, Yu Zhang, Rui Li, Yanxing Han, Yuan Lin, Jiandong Jiang

期刊论文

Direct acting antiviral-induced dynamic reduction of serum

Tung Huynh, Ke-Qin Hu

期刊论文

ROUTE DEVELOPMENT, ANTIVIRAL STUDIES, FIELD EVALUATION AND TOXICITY OF AN ANTIVIRAL PLANT PROTECTANT

期刊论文

Design, synthesis, and antiviral properties of 2-aryl-1H-benzimidazole-4-carboxamide derivatives

Xianjin LUO, Zhonglü ZHANG, Yutian YANG, Fei XUE, Naiyun XIU, Yuanbin SHE

期刊论文

ROUTE DEVELOPMENT, ANTIVIRAL STUDIES, FIELD EVALUATION AND TOXICITY OF AN ANTIVIRAL PLANT PROTECTANT

Wentao XU, Hao TIAN, Hongjian SONG, Yuxiu LIU, Yongqiang LI, Qingmin WANG

期刊论文

Occurrence, distribution and risk assessment of abused drugs and their metabolites in a typical urban

Peng Hu, Changsheng Guo, Yan Zhang, Jiapei Lv, Yuan Zhang, Jian Xu

期刊论文

Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

期刊论文

ANTIVIRAL EFFECTS OF BACTERIOCIN AGAINST ANIMAL-TO-HUMAN TRANSMITTABLE MUTATED SARS-COV-2: A SYSTEMATIC

期刊论文

Chinese expert consensus on oral drugs for the treatment of mature B-cell lymphomas (2020 edition)

期刊论文

nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleic acid drugs

Vaibhav Mundra, Ram I. Mahato

期刊论文

Current recommendations of managing HBV infection in preconception or pregnancy

null

期刊论文

Oral administration of

Sufen ZHAO,Yuanyuan JIA,Weiwei ZHANG,Lili WANG,Yunfei MA,Kedao TENG

期刊论文

Telomeric impact of conventional chemotherapy

null

期刊论文

关于联合国开发总署(UNDP)医农药工业在全球竞争中的技术升级研讨会介绍

李正名

期刊论文